The principal goals of this research program for the next four years are: (A) to complete the total synthesis of the anticancer agents (+)-tedanolide and (+)-13-deoxytedanolide, exploiting a unified synthetic strategy; (B) to devise an enantioselective total synthesis of the potent insecticidal agent (+)-nodulisporic acid; and (C) to achieve a total synthesis of the novel, architecturally challenging macrolide antibiotic sorangicin A. In addition, new innovative directions for our dithiane chemistry will indude: (D) reaction of dithianes with nitrogen-containing electrophiles (e.g., aziridine and allylic aziridines) for the development of new multicomponent assembly tactics; (E) reaction of dithianes with allylic epoxides, exploiting the SN2 and SN2' addition manifolds; and (F) merged SN2 and SN2' linchpin dithiane couplings. Finally, we will (G) showcase the multicomponent linchpin coupling of 2-lithio-2-trialkylsilyl-1,3-dithianes with aziridines and vinyl epoxides, respectively with expedient total syntheses of the Mantella alkaloid 223 AB and the aglycon of (+)-rimocidin. Beyond these specific synthetic objectives, a general, long-range goal of this program is the identification of the molecular architecture responsible for biological activity. Thus, as we develop an approach to each target structure, we will also prepare model compounds designed to permit the elucidation of structure-activity relationships.